HIV-infected children, youth, and adults have lower bone mineral density (BMD) than would be expected for HIV-uninfected people of similar age, weight and race. As the majority of perinatally HIV-infected U.S. children are entering or in adolescence, the potential for HIV-related impaired BMD during the adolescent peak of bone mass acquisition is of particular concern. The primary purpose of this study is to compare changes from pre-treatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment with placebo in HIV-infected children and adolescents.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Pre-treatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment versus placebo, as measured by Hologic bone densitometers [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]

Safety of of alendronate use as measured by the incidence of new hematology or chemistry laboratory values greater than or equal to Grade 3; signs or symptoms; or new cases of jaw osteonecrosis, atrial fibrillation, or non-healing fractures [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Effect of alendronate therapy on changes in HIV status (as measured by changes in viral load, CD4% and CDC disease category) and determination whether the changes in these outcomes correlate with changes in BMD [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Duration of detectable urinary alendronate in adolescent participants who have completed 48 and 96 weeks of alendronate therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Tablet taken once or twice daily. Dosage is dependent on participant's measured vitamin D levels

Placebo Comparator: 3

Participants will receive alendronate placebo tablet taken orally once weekly for 96 weeks

Drug: Alendronate placebo

Oral tablet taken once weekly

Dietary Supplement: Calcium carbonate/vitamin D

Tablet taken once or twice daily. Dosage is dependent on participant's measured vitamin D levels

Detailed Description:

Puberty is a time when the foundation is laid for healthy bone mass. Over the course of puberty, 26% of bone mass is established in the 4-year period of peak height velocity and up to 60% of adult peak bone mass is established. Factors that affect normal bone mineralization include calcium intake, vitamin D status, degree of physical and weight bearing activities, hormones, genetics, body weight, and general health and nutrition status. HIV-infected children, youth, and adults have lower bone mineral density (BMD) than would be expected for healthy people of similar age, weight, and race. As the majority of perinatally HIV-infected U.S. children are entering or in adolescence, the potential for HIV-related impaired BMD during the adolescent peak of bone mass acquisition is of particular concern. The purpose of this study is to compare changes from pretreatment levels of BMD of the lumbar spine after 24 and 48 weeks of alendronate treatment with placebo in HIV-infected children and adolescents.

This study will last approximately 144 weeks. Participants will be randomized into one of three groups.

Participants in Group 1 will receive alendronate for 96 weeks. Participants in Group 2 will receive alendronate for 48 weeks and alendronate placebo for an additional 48 weeks. Participants in Group 3 will receive placebo for 48 weeks followed by alendronate for 48 weeks. All three groups will be followed off treatment for an additional 48 weeks. All participants will receive vitamin D/calcium for the duration of the study.

There will be 13 study visits for each participant. They will occur at study entry and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144. A physical exam, targeted events history, and adherence questionnaire will occur at all visits. Blood and urine collection, Tanner stage assessment, DXA scan, and radiograph will occur at most visits. Participants will also complete a questionnaire about smoking behavior at screening. Participants will be contacted by telephone 7 times throughout the study at Weeks 1, 4, 28, 49, 52, 76, and 100 to screen for adverse events, assess adherence, and reinforce study instructions.

Information provided by adolescent participants about sexual activity, pregnancy, and smoking and alcohol use will not be shared without the participants' permission.

Eligibility

Ages Eligible for Study:

11 Years to 24 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Documentation of HIV-1 infection is defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. For studies conducted under an IND, all test methods should be FDA-approved if available. If FDA-approved methods are not available, test methods should be verified according to GCLP and approved by the IMPAACT central laboratory. Results documented in the clinical record from past testing may be used to satisfy the criteria for documentation of HIV-1 infection. More information on this criterion can be found in the protocol.

HIV-infected. Infection must have been acquired prior to puberty.

For participants receiving antiretroviral therapy, antiretroviral agents must be steady for at least 12 weeks prior to study entry and have a viral load less than 10,000 copies/mL

Lumbar spine DXA BMD z-score lower than -1.5 OR history of fragility fracture within the prior 12 months (regardless of DXA result). More information about this criterion can be found in the protocol.

Available for routine dental exam and care every 6 months

Demonstrates ability and willingness to swallow study medications

For females, participants must agree to use at least two forms of accepted contraceptives. More information about this criterion can be found in the protocol.

Exclusion Criteria:

Body weight of more than 300 lbs.

For female participants, received Depo-Provera for less than 1 full year during the year prior to study entry. More information about this criterion can be found in the protocol.

Anticonvulsant therapy

Proven growth hormone deficiency

Use of growth hormone in the 12 months prior to entry

Primary hyperparathyroidism

Hypoparathyroidism

Renal failure

Cushing syndrome

Active dental infection

Dental or periodontal disease that is expected to require more than basic restorative care

Hypocalcemia (less than the lower limit of normal established by the local laboratory in which it is performed)

Known abnormalities of the esophagus that delay esophageal emptying such as stricture or achalasia

25-OH vitamin D less than 10 ng/mL

Pregnant or breastfeeding

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00921557